A Diagnostic Biomarker for Pediatric Generalized Anxiety Disorder Using the Error-Related Negativity
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ORIGINAL ARTICLE
A Diagnostic Biomarker for Pediatric Generalized Anxiety Disorder Using the Error‑Related Negativity Gregory L. Hanna1 · Yanni Liu1 · Haley E. Rough1 · Mihir Surapaneni1 · Barbara S. Hanna1 · Paul D. Arnold2 · William J. Gehring3
© Springer Science+Business Media, LLC, part of Springer Nature 2020
Abstract The error-related negativity (ERN) is a negative deflection in the event-related potential following a mistake that is a putative biomarker of anxiety. The study assessed the ERN as a diagnostic biomarker using receiver operating characteristic (ROC) analyses in 96 cases with anxiety disorders (AD) and 96 matched healthy controls (HC) ages 8 to 18 years. Forty-one cases had generalized anxiety disorder (GAD); 55 cases had other anxiety disorders (OAD) without GAD. ERN amplitude was significantly increased in AD cases compared to HC. The area under the curve (AUC) in the ROC analysis was 0.64, indicating the ERN is an inadequate diagnostic test for AD altogether. The ERN was significantly increased in cases with either GAD or OAD compared to HC. The AUC in ROC analyses with GAD and OAD was 0.75 and 0.56, respectively, suggesting the ERN provides an adequate diagnostic test for GAD but not for OAD. Keywords Anxiety · Biomarker · Diagnosis · Error-related negativity · Pediatric · Receiver operating characteristic analysis
Introduction Anxiety disorders (AD) are the most common form of psychopathology in youth, with prevalence estimates ranging from 15 to 30% [1–3]. Youth with AD have an increased risk for subsequent anxiety and depressive disorders, illicit drug dependence, suicidal behavior, and educational underachievement as young adults [2, 4, 5]. The identification of mechanistic biomarkers that precede or develop concurrently with the onset of AD may advance our understanding of their pathogenesis, improve diagnostic and preventive strategies, and provide targets for cognitive, behavioral, and pharmacological treatments [6–8]. The error-related negativity (ERN or Ne)—a responselocked negative deflection in the event-related potential (ERP) that peaks within 80 ms after error commission—has * Gregory L. Hanna [email protected] 1
Department of Psychiatry, University of Michigan, Ann Arbor, MI 48109, USA
2
Mathison Centre for Mental Health Research and Education, University of Calgary, Calgary, AB T2N 4N1, Canada
3
Department of Psychology, University of Michigan, 4250 Plymouth Road, Ann Arbor, MI 48109‑5766, USA
been hypothesized to be a biomarker of pediatric AD [6, 7, 9–11]. Psychometric studies have demonstrated the ERN is stable across time and reliable across tasks [12]. The ERN has a heritability of 47% in youth, suggesting it may serve as an endophenotype in genetic studies of childhood psychopathology [13]. The ERN increases in magnitude throughout childhood and adolescence, indicating a prolonged maturation of the system underlying action monitoring [14]. The ERN has been described as a neural marker of errormonitoring processes [9–11], reinforcement learning [1
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